Proximo-Distal Patterning in the Drosophila Appendages

描述（由申请方提供）：动物发育取决于细胞命运和细胞潜能的连续细化。例如，胚胎干细胞是多能的，但它们的后代会根据它们感知到的细胞外信号和表达的内在因子逐渐呈现出更特定的命运。在机械水平上理解这一过程对于最终利用干细胞的医学潜力以及理解许多疾病（如癌症）都很重要，在这些疾病中，这一过程未能得到适当的调节。在本计画中，研究的模式系统是果蝇的附肢特化。一个目标是在分子水平上了解最初的腿和翅膀原基是如何在早期胚胎中建立起来的。第二个目标是表征顺式调节增强子元件在腿中近端-远端轴形成期间整合信号传导和转录因子输入的机制。第三个目标是研究表皮生长因子途径如何在腿的最远段建立位置信息。总之，这些目标将提供重要的见解，如何附件首先指定的腿中的最终位置信息是如何实现的。

DESCRIPTION (provided by applicant): Animal development depends on the successive refinement of cell fates and cell potentials. Embryonic stem cells, for example, are pluripotent but their descendents gradually take on more specific fates depending on the extracellular cues they perceive and intrinsic factors they express. Understanding this process at a mechanistic level is important for eventually harnessing the potential of stem cells for medicine, as well as for understanding many diseases, such as cancers, where this process fails to be properly regulated. In this project, the model system to be investigated is appendage specification in the fruit fly, Drosophila melanogaster. One goal is to understand, at a molecular level, how the initial leg and wing primordia become established in the early embryo. A second goal is to characterize the mechanism by which cis-regulatory enhancer elements integrate signaling and transcription factor inputs during the formation of the proximal- distal axis in the leg. A third goal is to investigate how the Epidermal Growth Factor pathway establishes positional information in the distal-most segments of the leg. Together, these Aims will provide significant insights into how appendages are first specified to how final positional information in the leg is achieved.